Variant 9-18622276-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001040272.6(ADAMTSL1):c.508G>A(p.Val170Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00241 in 1,613,976 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 9 hom. )

Consequence

ADAMTSL1
NM_001040272.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.87

Variant links:

Genes affected

ADAMTSL1 (HGNC:14632): (ADAMTS like 1) This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

ADAMTSL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058428645).

BP6

Variant 9-18622276-G-A is Benign according to our data. Variant chr9-18622276-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3042672.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL1	NM_001040272.6 linkuse as main transcript	c.508G>A	p.Val170Ile	missense_variant	5/29	ENST00000380548.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAMTSL1	ENST00000380548.9 linkuse as main transcript	c.508G>A	p.Val170Ile	missense_variant	5/29	5	NM_001040272.6	P1	Q8N6G6-3

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

331

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00262

AC:

657

AN:

250822

Hom.:

AF XY:

0.00291

AC XY:

395

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00474

Gnomad FIN exome

AF:

0.00180

Gnomad NFE exome

AF:

0.00316

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00243

AC:

3555

AN:

1461714

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

1885

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00505

Gnomad4 FIN exome

AF:

0.00178

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00233

GnomAD4 genome

AF:

0.00217

AC:

331

AN:

152262

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00315

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00204

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00293

AC:

356

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ADAMTSL1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 25, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.036

T;.;.;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.089

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0058

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

L;L;.;L;L

MutationTaster

Benign

0.98

N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.72

N;N;N;N;N

REVEL

Benign

0.092

Sift

Benign

0.12

T;T;T;T;T

Sift4G

Benign

0.083

T;T;T;T;T

Polyphen

0.0010

B;.;.;B;.

Vest4

0.17

MVP

0.46

MPC

0.056

ClinPred

0.020

GERP RS

2.7

Varity_R

0.043

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over